早老素1 E280A常染色体显性阿尔茨海默病家系中的血浆p-tau231：一项横断面和纵向队列研究。

Plasma p-tau231 in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: A cross-sectional and longitudinal cohort study.

作者信息

Malotaux Vincent, Ashton Nicholas J, Öhrfelt Annika, Chen Yinghua, Su Yi, Garcia-Ospina Gloria, Guzman-Martínez Claudia, Villegas-Lanau Andres, Gómez-Ramirez Johana, Giraldo-Chica Margarita, Aguillon David, Tirado Victoria, Baena Ana, Munoz Claudia, Acosta-Baena Natalia, Pruzin Jeremy J, Ghisays Valentina, Rios-Romenets Silvia, Vila-Castelar Clara, Martínez Jairo E, Giudicessi Averi, Tariot Pierre N, Zetterberg Henrik, Blennow Kaj, Reiman Eric M, Quiroz Yakeel T

机构信息

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Department of Psychiatry and Neurochemistry, Inst. of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.

出版信息

Alzheimers Dement. 2025 Jul;21(7):e70421. doi: 10.1002/alz.70421.

DOI:10.1002/alz.70421

PMID:40588692

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12208796/

Abstract

INTRODUCTION

Plasma phosphorylated tau (p-tau)-231 is a promising biomarker for Alzheimer's disease (AD), particularly in preclinical stages. We evaluated its diagnostic value in presenilin 1 (PSEN1) E280A mutation carriers versus non-carriers and compared it to p-tau217 and neurofilament light chain (NfL).

METHODS

We analyzed plasma p-tau231 in 722 carriers and 640 non-carriers (ages 18-75). Longitudinal data from 164 carriers and 132 non-carriers were available, with 137 carriers and 109 non-carriers having p-tau231, p-tau217, and NfL levels. Analyses used linear mixed effects models and restricted cubic splines.

RESULTS

E280A carriers had higher p-tau231 levels than non-carriers (9.0 ± 7.4 vs. 5.2 ± 3.4 pg/mL, P < 0.001). Baseline p-tau231 levels correlated with age, distinguishing carriers at age 23. Rates of change differed at age 19, ≈ 25 years before cognitive impairment. In a subset, p-tau231 changes differentiated carriers by age 20, earlier than p-tau217 and NfL.

DISCUSSION

Plasma p-tau231 is a sensitive biomarker for early AD detection and progression monitoring.

HIGHLIGHTS

Plasma phosphorylated tau (p-tau)231 levels are associated with age in presenilin 1 carriers and non-carriers. Baseline p-tau231 levels diverged between carriers and non-carriers at age 23. Plasma p-tau231 changes distinguished carriers by age 19, at very early stages. P-tau231 longitudinal changes differentiate carriers earlier than p-tau217 or neurofilament light chain.

摘要

引言

血浆磷酸化tau蛋白（p-tau）-231是阿尔茨海默病（AD）一种很有前景的生物标志物，尤其是在临床前期阶段。我们评估了其在早老素1（PSEN1）E280A突变携带者与非携带者中的诊断价值，并将其与p-tau217和神经丝轻链（NfL）进行比较。

方法

我们分析了722名携带者和640名非携带者（年龄18 - 75岁）的血浆p-tau231。可获取164名携带者和132名非携带者的纵向数据，其中137名携带者和109名非携带者有p-tau231、p-tau217和NfL水平。分析采用线性混合效应模型和受限立方样条。

结果

E280A突变携带者的p-tau231水平高于非携带者（9.0 ± 7.4 vs. 5.2 ± 3.4 pg/mL，P < 0.001）。基线p-tau231水平与年龄相关，在23岁时可区分携带者。在19岁时变化率不同，约在认知障碍出现前25年。在一个亚组中，p-tau231的变化在20岁时就能区分携带者，比p-tau217和NfL更早。